NR ADTP
AU Enari,M.; Flechsig,E.; Weissmann,C.
TI Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody
QU Proceedings of the National Academy of Sciences of the United States of America 2001 Jul 31; 98(16): 9295-9
PT journal article
AB Exposure of susceptible neuroblastoma N2a cells to mouse scrapie prions leads to infection, as evidenced by the continued presence of the scrapie form of the prion protein (PrPsc) and infectivity after 300 or more cell doublings. We find that exposure to phosphatidylinositol-specific phospholipase C (PIPLC) or to the monoclonal anti-prion protein (PrP) antibody 6H4 not only prevents infection of susceptible N2a cells but also cures chronically scrapie-infected cultures, as judged by the long-term abrogation of PrPsc accumulation after cessation of treatment. A nonpassaged, stationary infected culture rapidly loses PrPsc when exposed to the antibody or PIPLC, indicating that the PrPsc level is determined by steady state equilibrium between formation and degradation, and that depletion of the cellular form of PrP can interrupt the propagation of PrPsc. These findings encourage the belief that passive immunization may provide a therapeutic approach to prion disease.
MH Animal; Antibodies, Monoclonal/*immunology; Mice; Neuroblastoma/*metabolism/pathology; PrPsc Proteins/immunology/*metabolism; Support, Non-U.S. Gov't; Tumor Cells, Cultured
AD Medical Research Council Prion Unit, Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1PG, United Kingdom.
SP englisch
PO USA